Dialysis membranes of regenerated cellulose for hemodialysis in the form of flat films, tubular films, or hollow threads are known and are used in artificial kidneys, although some of their properties cause difficulties which have not yet been eliminated.
A dialysis membrane for hemodialysis with reduced thrombogenic activity, made of cellulose with chemically bound antithrombogenic compounds, is known from German Pat. No. 27 05 735. This dialysis membrane includes two or more layers of cellulose regenerated from cuoxam cellulose solutions, layers which were respectively obtained from separately supplied slits of a spinneret, whereby the cellulose layer on the blood side consists totally or partially of a modified cellulose which contains chemically bound antithrombogenic substances.
It has been previously proposed, however, in German Offenlegungsschrift No. 17 20 087 to reduce the danger of blood coagulation by reacting the polymer material of the membrane with an alkyl halide and then reacting the resulting material with an alkali salt of an antithrombogenic compound with cationic residues (e.g., haparin or a haparinoid compound). The possible alkyl halides include halogen alkyldialkylamines. Cellulose, primarily cellulose acetate, is included among possible polymers.
While dialysis membranes of synthetic or natural polymers when used in artifical kidneys can very easily cause blood coagulation, this is largely prevented by appropriate drug treatment or by the aforementioned special dialysis membranes. However, there is often a further problem with dialysis membranes of regenerated cellulose, which has not previously been solved satisfactorily. It has been demonstrated that a transient decline in leukocytes can occur at first in dialysis treatment of a kidney patient with cellulose membrane dialysers. This effect is known as leukopenia.
Leukopenia is a decline in the leukocyte (white blood cell) count in circulating blood. The number of white blood cells in humans is about 4,000 to 12,000 cells/mm.sup.3.
Leukopenia in dialysis is most strongly evident 15-20 minutes after its start, when neutrophils (leukocytes stainable with neutral or concurrently with acidic and basis dyes) can almost totally disappear. Within about an hour, the leukocyte count recovers almost to the starting value or exceeds the starting value.
If a new dialyzer is connected after the recovery of leukocytes, leukopenia of the same extent recurs.
Cellulose membranes provoke a marked leukopenia. Even if the clinical significance of the leukopenia is not scientifically explained, there still is the desire for a dialysis membrane for hemodialysis which does not exhibit the leukopenia effect, and also does not impair the other very desirable properties of dialysis membranes of regenerated cellulose.
Marked complement activation, in addition to leukopenia, has also been demonstrated in hemodialysis with membranes of regenerated cellulose. The complement system within blood serum is a complex plasma enzyme system, including many components, which serves in different ways as a defense against invading foreign cells (bacteria, etc.). If antibodies against the invading organism are present, the complement system can be activated, via the antibody complex, by the antigenic structures found on foreign cells or, by an alternate route, by means of specific surface features of the foreign cell. The complement system is based on many plasma proteins. Following activation these proteins interact specifically in a certain sequence and in the end a cytolytic complex is formed that destroys the foreign cell.
Peptides, which induce inflammation symptoms and occasionally may also have undesirable pathological consequences for the body, are released from separate components of the complement system.
It is assumed that the complement system activation by hemodialysis membranes made of regenerated cellulose occurs via the above-mentioned alternate route. Objectively this complement activation can be demonstrated by determination of fragments C3a and C5a among others. The following reports are cited in this regard: D. E. Chenoweth et al., Kidney International, Vol. 24, pp. 764 ff (1983), and D. E. Chenoweth, Asaio, Journal Vol. 7, pp. 44 ff (1984).